In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.

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Using [32P]P-Tyr-IgG and [32P]P-Tyr-casein phosphorylated by pp6O"-"c as substrates, studies on the phosphotyrosyl-protein phosphatase activity in human prostate gland indicate that it is associated with prostatic acid phosphatase. Evidence to support this conclusion include the following : (a) these two enzymatic activities co-purify to apparent homogeneity; (b) they co-migrated on polyacrylamide gel electrophoresis, ion-exchange and gel filtration chromatographies; (c) the exhibit identical thermostability; and (d) the phosphotyrosyl-protein phosphatase activity is sensitive to inhibition by p-nitrophenyl phosphate and by several classical inhibitors of prostatic acid phosphatase including I.(+)-tartrate, molybdate, vanadate and NaF. The purified enzyme exhibits high specificity towards phosphotyrosyl-proteins with little activity towards several phosphoseryl-proteins and phosphothreonyl-proteins examined. The present findings indicate that prostatic acid phosphatase may function in vivo as a phosphotyrosyl-protein phosphatase.Several transforming proteins, such as-pp60" coded by onc genes of viral or cellular origin have been shown to possess phosphotyrosyl-protein (P-Tyr-protein) kinase activity [ 1 -91. P-Tyr-protein kinase activity has also been shown to be associated with receptors for growth-promoting peptides, such as epidermal growth factor (EGF) [lo, 1 I], platelet-derived growth factor (PDGF) [12, 131 and insulin [14, 151. These findings have led to the hypothesis that phosphorylation at Tyr residues in proteins plays an important role in cellular transformation and in regulation of cellular growth [16,17].Several studies concerning P-Tyr-protein phosphatase activity in animal tissues have appeared recently. Alkaline phosphatases of animal and bacterial origin [18,19] and an acid phosphatase activity in the plasma membrane of human astrocytoma [20] have been reported to exhibit high specificity towards P-Tyr-histones. On the other hand, various P-Tyrprotein phosphatases lacking activity towards low-molecularweight non-protein phosphoesters, such asp-nitrophenyl phosphate (pNpP), have also been described [21-241. In this communication we examine P-Tyr-protein phosphatase activity in human prostate gland. The results indicate that the major active species of P-Tyr-protein phosphatase activity in this tissue is associated with acid phosphatasese, which has served as a useful biological marker of metastatic prostatic carcinoma for the last four decades [25 -281.